Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis

Abstract

Inflammatory bowel disease is a complex collection of disorders. Microbial dysbiosis as well as exposure to toxins including xenoestrogens are thought to be risk factors for inflammatory bowel disease development and relapse. Bisphenol-A has been shown to exert estrogenic activity in the colon and alter intestinal function, but the role that xenoestrogens, such as bisphenol-A , play in colonic inflammation has been previously described but with conflicting results. We investigated the ability of bisphenol-A to exacerbate colonic inflammation and alter microbiota metabolites derived from aromatic amino acids in an acute dextran sulfate sodium-induced colitis model. Female C57BL/6 mice were ovariectomized and exposed to bisphenol-A daily for 15 days. Disease activity measures include body weight, fecal consistency, and rectal bleeding. Colons were scored for inflammation, injury, and nodularity. Alterations in the levels of microbiota metabolites derived from aromatic amino acids known to reflect phenotypic changes in the gut microbiome were analyzed. Bisphenol-A exposure increased mortality and worsened disease activity as well as inflammation and nodularity scores in the middle colon region following dextran sulfate sodium exposure. Unique patterns of metabolites were associated with bisphenol-A consumption. Regardless of dextran sulfate sodium treatment, bisphenol-A reduced levels of tryptophan and several metabolites associated with decreased inflammation in the colon. This is the first study to show that bisphenol-A treatment alone can reduce microbiota metabolites derived from aromatic amino acids in the colon which may be associated with increased colonic inflammation and inflammatory bowel disease. Impact statement As rates of inflammatory bowel disease rise, discovery of the mechanisms related to the development of these conditions is important. Environmental exposure is hypothesized to play a role in etiology of the disease, as are alterations in the gut microbiome and the metabolites they produce. This study is the first to show that bisphenol-A alone alters tryptophan and microbiota metabolites derived from aromatic amino acids in a manner consistent with autoimmune diseases, specifically inflammatory bowel diseases, regardless of dextran sulfate sodium treatment. These findings indicate a potential mechanism by which bisphenol-A negatively affects gut physiology to exacerbate inflammation.

Breast Cancer and Its Relationship with the Microbiota

“…Some endocrine compounds could induce alterations in the gut microbiota and the metabolites they produce, which may be associated with increased inflammation [97]. …”

Neurochemical characterization of the enteric neurons within the porcine jejunum in physiological conditions and under the influence of bisphenol A (BPA)

“…It should be noted that previous studies have reported that BPA may change intestinal nociception and impair the gut barrier function . It is also known that this substance can alter intestinal microbiota metabolism and is involved in pathogenesis of the inflammatory bowel disease . However, knowledge concerning BPA‐induced changes in the neurochemical characterization of the enteric neurons is rather scanty and limited to the ENS in the duodenum and ileum 4.…”

“…1,30 It is also known that this substance can alter intestinal microbiota metabolism and is involved in pathogenesis of the inflammatory bowel disease. 5,31,32 However, knowledge concerning BPA-induced changes in the neurochemical characterization of the enteric neurons is rather scanty and limited to the ENS in the duodenum and ileum 4. Therefore, the aim of this study was to investigate the changes caused by various doses of BPA on the ENS in the jejunum-the part of the intestine where the bulk of this substance occurring in the food is absorbed.…”

Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases

“…Some Bifidobacterium strains have been shown to exert health-promoting effects and is included in a number of probiotic foods and supplements [97]. DeLuca et al (2018) [46] used a dextran sulphate sodium-induced colitis model in female C57BL/6 mice and found that BPA exposure at 50 µg/kg/day negatively affects gut physiology by reducing microbiota metabolites derived from aromatic amino acids, which might be associated with autoimmune diseases, specifically with inflammatory bowel disease. This dose was selected because it is the EPA reference dose for BPA.…”